Achieving operational safety of chemical processes while operating them in an economically‐optimal manner is a matter of great importance. Our recent work integrated process safety with process control by incorporating safety‐based constraints within model predictive control (MPC) design; however, the safety‐based MPC was developed with a centralized architecture, with the result that computation time limitations within a sampling period may reduce the effectiveness of such a controller design for promoting process safety. To address this potential practical limitation of the safety‐based control design, in this work, we propose the integration of a distributed model predictive control architecture with Lyapunov‐based economic model predictive control (LEMPC) formulated with safety‐based constraints. We consider both iterative and sequential distributed control architectures, and the partitioning of inputs between the various optimization problems in the distributed structure based on their impact on process operational safety. Moreover, sufficient conditions that ensure feasibility and closed‐loop stability of the iterative and sequential safety distributed LEMPC designs are given. A comparison between the proposed safety distributed EMPC controllers and the safety centralized EMPC is demonstrated via a chemical process example. © 2017 American Institute of Chemical Engineers AIChE J, 63: 3404–3418, 2017